Abstract

Background

Non-small cell lung cancer (NSCLC) is one of the most frequent malignancies and has
a high mortality rate due to late detection and lack of efficient treatments. Identifying
novel drug targets for this indication may open the way for new treatment strategies.
Comparison of gene expression profiles of NSCLC and normal adjacent tissue (NAT) allowed
to determine that 5-alpha-reductase type I (SRD5A1) was up-regulated in NSCLC compared
to NAT. This raised the question whether SRD5A1 was involved in sustained proliferation
and survival of NSCLC.

Methods

siRNA-mediated silencing of SRD5A1 was performed in A549 and NCI-H460 lung cancer
cell lines in order to determine the impact on proliferation, on distribution during
the different phases of the cell cycle, and on apoptosis/necrosis. In addition, lung
cancer cell lines were treated with 4-azasteroids, which specifically inhibit SRD5A1
activity, and the effects on proliferation were measured. Statistical analyses using
ANOVA and post-hoc Tamhane-T2-test were performed. In the case of non-parametric data,
the Kruskal-Wallis test and the post-hoc Mann-Whitney-U-test were used.

Results

The knock-down of SRDA51 expression was very efficient with the SRD5A1 transcripts
being reduced to 10% of control levels. Knock-down efficiency was furthermore confirmed
at the protein level. However, no effect of SRD5A1 silencing was observed in the proliferation
assay, the cell cycle analysis, and the apoptosis/necrosis assay. Treatment of lung
cancer cell lines with 4-azasteroids did not significantly inhibit proliferation.

Conclusions

In summary, the results suggest that SRD5A1 is not a crucial enzyme for the sustained
proliferation of NSCLC cell lines.